{"id":3301,"date":"2024-12-13T13:49:58","date_gmt":"2024-12-13T04:49:58","guid":{"rendered":"https:\/\/misterx95.myds.me\/wordpress\/?p=3301"},"modified":"2024-12-13T13:49:59","modified_gmt":"2024-12-13T04:49:59","slug":"journal-club-2024-12-13","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=3301","title":{"rendered":"Journal club 2024.12.13"},"content":{"rendered":"\n<p>Cell.\u00a02024 Oct 24:S0092-8674(24)01149-8.<\/p>\n\n\n\n<p>&nbsp;doi: 10.1016\/j.cell.2024.10.001.&nbsp;Online ahead of print.<\/p>\n\n\n\n<h1>Structure-guided discovery of bile acid derivatives for treating liver diseases without causing itch<\/h1>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Yang+J&amp;cauthor_id=39476841\">Jun Yang<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-1\">1<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Zhao+T&amp;cauthor_id=39476841\">Tianjun Zhao<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-2\">2<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Fan+J&amp;cauthor_id=39476841\">Junping Fan<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-3\">3<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Zou+H&amp;cauthor_id=39476841\">Huaibin Zou<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-4\">4<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Lan+G&amp;cauthor_id=39476841\">Guangyi Lan<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-5\">5<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Guo+F&amp;cauthor_id=39476841\">Fusheng Guo<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-1\">1<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Shi+Y&amp;cauthor_id=39476841\">Yaocheng Shi<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-3\">3<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Ke+H&amp;cauthor_id=39476841\">Han Ke<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-3\">3<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Yu+H&amp;cauthor_id=39476841\">Huasheng Yu<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-6\">6<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Yue+Z&amp;cauthor_id=39476841\">Zongwei Yue<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-1\">1<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Wang+X&amp;cauthor_id=39476841\">Xin Wang<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-7\">7<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Bai+Y&amp;cauthor_id=39476841\">Yingjie Bai<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-7\">7<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Li+S&amp;cauthor_id=39476841\">Shuai Li<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-8\">8<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Liu+Y&amp;cauthor_id=39476841\">Yingjun Liu<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-8\">8<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Wang+X&amp;cauthor_id=39476841\">Xiaoming Wang<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-8\">8<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Chen+Y&amp;cauthor_id=39476841\">Yu Chen<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-9\">9<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Li+Y&amp;cauthor_id=39476841\">Yulong Li<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-10\">10<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Lei+X&amp;cauthor_id=39476841\">Xiaoguang Lei<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39476841\/#full-view-affiliation-11\">11<\/a><\/sup><\/p>\n\n\n\n<ul id=\"full-view-identifiers\">\n<li>PMID:&nbsp;<strong>39476841<\/strong><\/li>\n\n\n\n<li>DOI:&nbsp;<a target=\"_blank\" rel=\"noreferrer noopener\" href=\"https:\/\/doi.org\/10.1016\/j.cell.2024.10.001\">10.1016\/j.cell.2024.10.001<\/a><\/li>\n<\/ul>\n\n\n\n<h2>Abstract<\/h2>\n\n\n\n<p>Chronic itch is a debilitating symptom profoundly impacting the quality of life in patients with liver diseases like cholestasis. Activation of the human G-protein coupled receptor, MRGPRX4 (hX4), by bile acids (BAs) is implicated in promoting cholestasis itch. However, the detailed underlying mechanisms remain elusive. Here, we identified 3-sulfated BAs that are elevated in cholestatic patients with itch symptoms. We solved the cryo-EM structure of hX4-Gq in a complex with 3-phosphated deoxycholic acid (DCA-3P), a mimic of the endogenous 3-sulfated deoxycholic acid (DCA-3S). This structure revealed an unprecedented ligand-binding pocket in MRGPR family proteins, highlighting the crucial role of the 3-hydroxyl (3-OH) group on BAs in activating hX4. Guided by this structural information, we designed and developed compound 7 (C7), a BA derivative lacking the 3-OH. Notably, C7 effectively alleviates hepatic injury and fibrosis in liver disease models while significantly mitigating the itch side effects.<\/p>\n\n\n\n<p><strong>Keywords:\u00a0<\/strong>3-sulfonated bile acids; MRGPRX4; OCA; bile acids; cholestatic pruritus; cryo-EM structure; deoxycholic acid; farnesoid X receptor; liver diseases; non-alcoholic steatohepatitis.<\/p>\n\n\n\n<div class=\"wp-block-file\"><object class=\"wp-block-file__embed\" data=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2024\/12\/Structure-guided-discovery-of-Bile-acid-Derivatives.pdf\" type=\"application\/pdf\" style=\"width:100%;height:600px\" aria-label=\"Embed of Structure-guided-discovery-of-Bile-acid-Derivatives.\"><\/object><a id=\"wp-block-file--media-a9ac6b11-636d-409d-9883-2297c70f4db1\" href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2024\/12\/Structure-guided-discovery-of-Bile-acid-Derivatives.pdf\">Structure-guided-discovery-of-Bile-acid-Derivatives<\/a><a href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2024\/12\/Structure-guided-discovery-of-Bile-acid-Derivatives.pdf\" class=\"wp-block-file__button wp-element-button\" download aria-describedby=\"wp-block-file--media-a9ac6b11-636d-409d-9883-2297c70f4db1\">Download<\/a><\/div>\n","protected":false},"excerpt":{"rendered":"<p>Cell.\u00a02024 Oct 24:S0092-8674(24)01149-8. &nbsp;doi: 10.1016\/j.cell.2024.10.001.&nbsp;Online ahead of print. Structure-guided discovery of bile acid derivatives for treating liver diseases without causing itch Jun Yang\u00a01,\u00a0Tianjun Zhao\u00a02,\u00a0Junping Fan\u00a03,\u00a0Huaibin Zou\u00a04,\u00a0Guangyi Lan\u00a05,\u00a0Fusheng Guo\u00a01,\u00a0Yaocheng Shi\u00a03,\u00a0Han Ke\u00a03,\u00a0Huasheng Yu\u00a06,\u00a0Zongwei Yue\u00a01,\u00a0Xin Wang\u00a07,\u00a0Yingjie Bai\u00a07,\u00a0Shuai Li\u00a08,\u00a0Yingjun Liu\u00a08,\u00a0Xiaoming Wang\u00a08,\u00a0Yu Chen\u00a09,\u00a0Yulong Li\u00a010,\u00a0Xiaoguang Lei\u00a011 Abstract Chronic itch is a debilitating symptom profoundly impacting the quality of life in patients [&hellip;]<\/p>\n","protected":false},"author":19,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3301"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/19"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3301"}],"version-history":[{"count":1,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3301\/revisions"}],"predecessor-version":[{"id":3303,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3301\/revisions\/3303"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3301"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3301"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3301"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}